The purpose of this study is to test the safety and immunogenicity of MVA-BN-Filo and Ad26.ZEBOV as heterologous prime-boost vaccine regimens in healthy adult participants.

This first-in-human study consists of 2 parts: 1) The main study, which is randomized, placebo-controlled, observer-blind; 2) A sub-study, which is open-label, uncontrolled, non-randomized study evaluating the safety, tolerability, and immunogenicity of MVA-BN-Filo and Ad26.ZEBOV administered in different sequences and schedules to healthy adult participants. The study consists of a Screening period (up to 28 days in the main study and up to 56 days in the sub-study), a vaccination period in which participants will be vaccinated at baseline (Day 1) followed by a boost on Day 15, 29 or 57, and a post-boost follow-up until all participants have had their 21-day post-boost visit (Day 36, 50 or Day 78). The total duration of the study will be about 1 year for participants who received vaccine and about 3 months for participants who received placebo. Safety will be monitored during the study.

Inclusion Criteria:

• Must be healthy on the basis of physical examination, medical history, and the investigator's clinical judgment
• Women of childbearing potential must have a negative serum β-human chorionic gonadotropin pregnancy test at screening, a negative urine pregnancy test immediately prior to each study vaccine administration, and practice adequate birth control measures from 28 days before the prime vaccination until at least 3 months after the boost vaccination as specified in the study protocol. If not heterosexually active at screening, must agree to practice adequate birth control measures if they become heterosexually active during their participation in the study (from screening onwards until at least 3 months after the boost vaccination). Agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction from screening onwards until at least 3 months after the boost vaccination
• Women of non-childbearing potential, defined as postmenopausal (>45 years of age with amenorrhea for ≥2 years or any age with amenorrhea for ≥6 months and serum follicle-stimulating hormone [FSH] >40 mIU/mL) or surgically sterile (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), are not required to use the birth control methods as specified in the study protocol
• A man who is sexually active with a woman of childbearing potential and who has not had a vasectomy must agree to use a double-barrier method of birth control, such as either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. In case the female partner is using an adequate method of birth control, a single-barrier method of birth control for the male subject is acceptable. Men must also agree not to donate sperm from screening onwards until at least 3 months after the boost vaccination
• Must be available and willing to participate for the duration of the study visits and follow-up, provide verifiable identification, and have a means to be contacted

Exclusion Criteria:

• Has been vaccinated with a candidate Ebola vaccine
• Has been diagnosed with Ebola disease or exposed to Ebola including travel to West Africa in the last 12 months. West Africa includes but is not limited to the countries of Guinea, Liberia, Mali, and Sierra Leone
• Has received any Ad26- or MVA-based candidate vaccine in the past
• Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines), including known allergy to egg or aminoglycosides
• A woman who is pregnant or breast-feeding, or planning to become pregnant while enrolled in the study or within 3 months after the boost vaccination
• History of diabetes mellitus type 1 or type 2, including cases controlled with diet alone; thyroidectomy, or thyroid disease requiring medication during the last 12 months; uncontrolled hypertension as defined in the study protocol; or, major psychiatric illness and/or substance abuse problems during the past 12 months that in the opinion of the investigator would preclude participation